The third signal in T cell-mediated autoimmune disease?

被引:38
作者
Darabi, K
Karulin, AY
Boehm, BO
Hofstetter, HH
Fabry, Z
LaManna, JC
Chavez, JC
Tary-Lehmann, M
Lehmann, PV
机构
[1] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44118 USA
[2] Case Western Reserve Univ, Dept Anat, Cleveland, OH 44118 USA
[3] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA
[4] Univ Hosp Ulm, Endocrinol Sect, Ulm, Germany
关键词
D O I
10.4049/jimmunol.173.1.92
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The initial event in the pathogenesis of autoimmune disease is thought to be the priming of naive autoreactive T cells by an infection with a cross-reactive microorganism. Although such cross-reactive priming should be a common event, autoimmune disease does not frequently develop. This situation is reflected after the immunization of C57BL/6 mice with the neuroantigen myelin oligodendrocyte glycoprotein (MOG) with CFA, which primes a type 1 T cell response but does not lead to clinical or histological manifestation of experimental allergic encephalomyelitis unless pertussis toxin is injected in addition. We show in this study that, in MOG:CFA-primed mice, the autoimmune CNS pathology develops after intracerebral deposition of TLR9-activating CpG oligonucleotides, but not following non-CpG oligonucleotide injection or after aseptic cryoinjury of the brain. Thus, access of primed MOG-specific Th1 cells to the uninflamed CNS or to CNS undergoing sterile inflammation did not suffice to elicit autoimmune pathology; only if the APC in the target organ were activated in addition by the TLR9-stimulating microbial product did they exert local effector functions. The data suggest that such licensing of APC in the target organ by microbial stimuli represents a checkpoint for functional self-tolerance. Therefore, microorganisms unrelated to the cross-reactive agent that primes the autoreactive T cells could dictate the onset and exacerbation of autoimmune diseases.
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页码:92 / 99
页数:8
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